Cytokine CCL7-mediated activation of mesenchymal stem cells to promote urinary continence via periurethral fibroblasts mechanism

Abstract Stress urine incontinence (SUI) is common in middle-aged and older people, and there are no effective treatments. In our investigation, MSC secretion activated periurethral fibroblasts. MSC secretion concentrate improves stress urinary incontinence in animal models. Our work indicated that CCL7 recruits activated MSC cells. This study compared the omics expression of associated secretions after CCL7 was added to activate mesenchymal stem cells and the molecular regulatory mechanisms involved. Periurethral fibroblasts were immortalised from patients with urine incontinence and anterior pelvic prolapse. Proteomic analysis was used to examine the composition of conditioned media obtained from bone marrow stromal cells and to study the link between fibroblast proliferation and migration and, eventually, signal route incurred changes. We identified the most plausible PI3k/AKT signal transduction route for activating periurethral fibroblasts generated by CCL7 and MSC secretions. CCL7+MSC-CM promoted collagen production, proliferation, and migration of periurethral fibroblasts better than MSC-CM. PI3k/AKT-related pathways linked with increased fibroblast proliferation and migration were activated. After CCL7 intervention, MSC-CM activated periurethral fibroblasts through PI3k/AKT. EFNA1 may play a critical role in the proliferation of periurethral fibroblasts, contributing to urinary continence and architecture.